The present invention relates to a process for preparing 2,2,6,6-tetrahalocyclohexaneimine derivatives having the formula (I): ##STR1## wherein R is a hydrogen atom, a linear or branched alkyl group, or a substituted or unsubstituted aromatic group, and each X is a halogen atom, which are starting materials of 2,6-dihaloaniline derivatives. The 2,6-dihaloaniline derivatives having the formula (II): ##STR2## wherein R and X are as defined above, are intermediates of substituted phenylacetic acids suitable for use of an antiphlogistic, analgesic or antipyretic, as shown in Japanese Examined Patent Publication No. 23418/1967. More particularly, the present invention relates to a process for preparing 2,2,6,6-tetrahalocyclohexaneimine derivatives having the formula (I) which comprises subjecting to dehydration condensation of a 2,2,6,6-tetrahalocyclohexanone with a primary amine or ammonia.
Also, the present invention relates to a process for preparing 2,6-dihaloaniline derivatives having the formula (II), and more particularly to a process for preparing 2,6-dihaloaniline derivatives (II) which comprises subjecting to dehydrohalogenation of the 2,2,6,6-tetrahalocyclohexaneimine derivatives (I).
Further, the present invention relates to an N-phenyl-2,2,6,6-tetrahalocyclohexaneimine having the formula (III): ##STR3## wherein each X ia a halogen atom. The novel compound (III) is a starting material of an N-phenyl-2,6-dihaloaniline which is one of intermediates of substituted phenylacetic acids suitable for use of antiphlogistic, analgesic, antipyretic, and the like.
The 2,2,6,6-tetrahalocyclohexaneimine derivative (I) is especially useful as a starting material of the 2,6-dihaloaniline derivative (II).
Also, the 2,6-dihaloaniline derivative (II) is useful as an intermediate of the substituted phenylacetic acid useful as drugs or agricultural chemicals. Particularly, as disclosed in Japanese Examined Patent Publication No. 23418/1967, the derivative (II) is useful as an intermediate of one of substituted phenylacetic acids, having the formula (IV): ##STR4## wherein R.sup.1 is a lower alkyl group, a lower alkoxyl group, a halogen atom of fluorine, chlorine or bromine, or a trifluoromethyl group, each R.sup.2 and R.sup.3 is a hydrogen atom, a lower alkyl group, a lower alkoxyl group or a halogen atom of fluorine, chlorine or bromine, R.sup.4 is a hydrogen atom, a lower alkyl group, a lower alkoxyl group, a halogen atom of fluorine, chlorine or bromine or a trifluoromethyl group, and each R.sup.5 and R.sup.6 is a hydrogen atom, a lower alkyl group or a benzyl group.
It has been known that a 2,2,6,6-tetrahalocyclohexanone is reacted with an alcoholate to give a 2-alkoxy-3-halophenol, and also it is dehydrohalogenated with an amine to give a 2,6-dihalophenol. However, it has not been known that the 2,6,6,6-tetrahalocyclohexanone is subjected to dehydration condensation with the amine, e.g. it is reacted with ammonia or a primary amine to produce a ketimine.
On the other hand, the 2,6-dihaloaniline derivative (II) can be prepared by various known processes. For example, Japanese Examined Patent Publication No. 23418/1967 discloses a process for preparing the 2,6-dihaloaniline derivative and a process for preparing a substituted phenylacetic acid therefrom, as shown in the following reaction formulae: ##STR5## wherein X is bromine atom or iodine atom. In the above reaction formulae, a 2,6-dihaloaniline is produced by halogenating an N-acetylsulfanil chloride to give a 2,6-dihalo-N-acetylsulfanil chloride and hydrolyzing the obtained compound to eliminate acetyl group and chlorosulfonyl group therefrom. Then, the obtained 2,6-dihaloaniline is condensed with a halide such as iodobenzene or bromobenzene according to Ullmann reaction in the presence of copper powder and potassium carbonate at high temperature to give the 2,6-dihaloaniline derivatives.
In the above-mentioned process, for preparing the 2,6-dihaloaniline derivatives, there are some problems that the yield is low or wastes are produced in a large amount since several steps are required for obtaining the 2,6-dihaloaniline; in case of using the iodine compound as the halide for obtaining the 2,6-dihaloaniline derivatives, the cost of products becomes high because the iodine compounds are expensive; in case of using the bromo compound, 2-chloro-6-bromoaniline is generated as a by-product, consequently, very much time and labor are required in order to separate and purify the desired product.
It is an object of the present invention to provide a process for preparing the 2,2,6,6-tetrahalocyclohexaneimine derivative (I) from inexpensive starting materials in high yield through a few steps. The 2,2,6,6-tetrahalocyclohexaneimine derivatives (I) are very useful as starting materials for obtaining the 2,6-dihaloaniline derivatives (II) inexpensively in high purity.
It is a further object of the present invention is to provide a process for preparing the 2,6-dihaloaniline derivative (II) from inexpensive starting materials in high yield and high purity through a few steps. The 2,6-dihaloaniline derivatives (II) are very useful as intermediates of the substituted phenylacetic acid useful as drugs or agricultural chemicals.
The N-phenyl-2,6-dihaloaniline, for instance, N-phenyl-2,6-dichloroaniline, is prepared by the following reaction formula, as disclosed in Japanese Examined Patent Publication No. 23418/1967. ##STR6## wherein X is bromine atom or iodine atom. The 2,6-dichloroaniline is condensed with iodobenzene or bromobenzene according to Ullmann reaction in the presence of a catalyst of potassium carbonate copper powder to give N-phenyl-2,6-dichloroaniline. However, the process have defects that the cost of products becomes high because 2,6-dichloroaniline and iodobenzene are expensive, when using the compounds. Also, when using bromobenzene, though bromobenzene is relatively cheap, N-phenyl-2-chloro-6-bromoaniline is generated as a by-product. Consequently, very much time and labor are required for purification of the desired products.
It is a still further object of the present invention is to provide an N-phenyl-2,2,6,6-tetrahalocyclohexaneimine having the formula (III): ##STR7## wherein X is a halogen atom. There can be provided from the compound (III) an N-phenyl-2,6-dihaloaniline such as N-phenyl-2,6-dichloroaniline at a low cost in high purity.
These and other objects of the present invention will become apparent from the following description.